Krabbe’s disease in two West Highland White terriers

Mt, Capucchio; Prunotto, Marco; Lotti, D.; Valazza, Alberto; Galloni, M.; Dore, Bruno Emilio; Pregel, Paola; Amedeo, S.; Catalano, D; Cornaglia, E.; Schiffer, Davide

doi:10.5414/npp27295

Cited by 2 publications

(1 citation statement)

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“…These include dogs [70,71], cats [72], and the rhesus monkey [73]. Although none of these have been used to study myelin repair, the canine and primate models as large animal models, provide the opportunity to scale-up remyelination therapies.…”

Section: The Twitcher Mousementioning

confidence: 99%

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

2011

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The leukodystrophies are rare and serious genetic disorders of the central nervous system that primarily affect children who frequently die early in life or have significantly delayed motor and mental milestones that result in long-term disability. Although with some of these disorders, early intervention with bone marrow or cord blood transplantation has been proven useful, it has not yet been determined that such therapies promote myelin repair of the central nervous system. Research on experimental therapies aimed at myelin repair is aided by the ability to test cell replacement strategies in genetic models in which the mutations and neuropathology match the human disorder. Thus, models exist of Pelizaeus-Merzbacher disease and the lysosomal storage disorder, Krabbe disease, which reflect the clinical and pathological course of the human disorders. Collectively, animals with mutations in myelin genes are called the myelin mutants, and they include rodent models such as the shiverer mouse that have been extensively used to study myelination by exogenous cell transplantation. These studies have encompassed many permutations of the age of the recipient, type of transplanted cell, site of engraftment, and so forth, and they offer hope that the scaling up of myelin produced by transplanted cells will have clinical significance in treating patients. Here we review these models and discuss their relative importance and use in such translational approaches. We discuss how grafts are identified and functional outcomes are measured. Finally, we briefly discuss the cells that have been successfully transplanted, which may be used in future clinical trials.

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Section: The Twitcher Mousementioning

confidence: 99%

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

2011

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Lysosomal storage diseases. Sphingolipidoses – leukodystrophy

Gorbunova,

Buchinskaia,

Vechkasova

et al. 2024

Pediatr (SPb)

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Epidemiological, clinical, biochemical and molecular-genetic characteristics of lysosomal leukodystrophies are presented, which include metachromatic leukodystrophy, globoid cell leukodystrophy, or Krabbe disease, combined saposin and multiple sulfatase deficiency. The pathogenesis of metachromatic and globoid cell leukodystrophy is based on hereditary deficiency of two lysosomal enzymes — arylsulfatase A and galactocerebrosidase, accompanied by excessive accumulation of galactosphingosulfatides and galactosylceramide, respectively. The consequence of this is demyelination of the central and peripheral nervous system and damage to the white matter of the brain. Experimental models show effectiveness of pathogenetic approaches, such as hematopoietic stem cell transplantation and gene therapy, only if treatment is started before the development of severe neurological anomalies. In this regard, neonatal screening methods for these two forms of leukodystrophy are being developed, which have been particularly successful in the early diagnosis of Krabbe disease. For each of the two leukodystrophies (metachromatic and globoid cell), rare genetic variants have been described due to the absence of activator proteins for arylsulfatase A and galactocerebrosidase (saposins B and C), respectively, due to specific mutations in the gene of the precursor of saposins, prosaposin (PSPA). Mutations in the PSPA gene resulting in the absence of all four saposins (A, D, C and D) are the cause of combined saposin deficiency, characterized by the development of severe neurological disorders soon after birth and death before the age of 1 year. The pathogenesis of multiple sulfatase deficiency is based on the accumulation of sulfatides, sulfated glycosaminoglycans, sphingolipids, and steroid sulfates, caused by inactivating mutations in the SUMF1 gene of the sulfatase-modifying factor 1 involved in the biosynthesis of all sulfatases. The disease is characterized by a combined manifestation of metachromatic leukodystrophy and mucopolysaccharidosis in combination with severe neurological disorders, mental retardation, sensorineural hearing loss and ichthyosis. Clinical guidelines for the diagnosis, management and therapy of combined saposin and multiple sulfatase deficiency have not yet been developed. The article presents a description of a clinical case of Krabbe disease in a child observed in the medical genetic center of St. Petersburg.

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Krabbe’s disease in two West Highland White terriers

Cited by 2 publications

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The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

Lysosomal storage diseases. Sphingolipidoses – leukodystrophy

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